Department of Urology and Pediatric Urology, University Hospital, Philipps-University Marburg, Baldingerstr. 1, 35043, Marburg, Germany.
Immunol Res. 2022 Oct;70(5):698-707. doi: 10.1007/s12026-022-09302-y. Epub 2022 Jun 23.
Sepsis causes a myriad of immunological reactions that result in life-threatening alterations in the human body. Immunosuppression in sepsis is partly attributed to the programmed death receptor (PD-1) and its associated ligand (PD-L1) via the regulation of lymphocytes and neutrophils. Although the soluble forms of these proteins (i.e., sPD-1 and sPD-L1, respectively) are recognized as possible sepsis biomarkers, their functional implications are yet to be elucidated. Our research assessed the correlation between sPD-1 and sPD-L1 and blood mRNA markers and sepsis outcome. Blood samples of septic patients of urogenital origin versus control patients (both groups: n = 18) were analyzed. Blood serum sPD-1 and sPD-L1 levels were determined using the enzyme-linked immunosorbent assay (ELISA). The whole blood mRNA concentrations of PD-1, PD-L1, neutrophil markers (CEACAM8 and MPO), and T-lymphocyte markers (TCRβ, CD4 and CD8) were determined via reverse transcriptase quantitative PCR (RT-qPCR). sPD-L1 levels were significantly increased in septic patients when compared to the controls, whereas sPD-1 levels were unaltered. Patients with high sPD-L1 levels, as dichotomized to the median, had a significantly shorter survival rate than those with low sPD-L1 levels. The sensitivity/specificity characteristics of sPD-L1 proved significant for sepsis detection. Furthermore, sPD-L1 correlated with the mRNA concentrations of PD-L1, CEACAM, and MPO, as well as major inflammatory markers (C-reactive protein and procalcitonin). However, sPD-L1 negatively correlated with TCRβ, CD4, and CD8 mRNAs. sPD-L1 was found to be significantly increased in septic patients. Notably, sPD-L1 correlated with PD-L1 mRNA and neutrophil markers and was indicative of adverse outcomes.
脓毒症引起多种免疫反应，导致人体发生危及生命的改变。脓毒症中的免疫抑制部分归因于程序性死亡受体 (PD-1) 及其相关配体 (PD-L1) 通过调节淋巴细胞和中性粒细胞。尽管这些蛋白质的可溶性形式（即 sPD-1 和 sPD-L1）分别被认为是可能的脓毒症生物标志物，但它们的功能意义仍有待阐明。我们的研究评估了 sPD-1 和 sPD-L1 与血液 mRNA 标志物和脓毒症结局之间的相关性。分析了来自泌尿生殖道来源的脓毒症患者和对照患者（两组：n = 18）的血液样本。使用酶联免疫吸附测定法 (ELISA) 测定血清 sPD-1 和 sPD-L1 水平。通过逆转录定量 PCR (RT-qPCR) 测定全血中 PD-1、PD-L1、中性粒细胞标志物 (CEACAM8 和 MPO) 和 T 淋巴细胞标志物 (TCRβ、CD4 和 CD8) 的 mRNA 浓度。与对照组相比，脓毒症患者的 sPD-L1 水平显着升高，而 sPD-1 水平没有变化。中位数分为高 sPD-L1 水平的患者的生存率显着低于低 sPD-L1 水平的患者。sPD-L1 的敏感性/特异性特征对脓毒症检测具有重要意义。此外，sPD-L1 与 PD-L1、CEACAM 和 MPO 的 mRNA 浓度以及主要炎症标志物（C 反应蛋白和降钙素原）相关。然而，sPD-L1 与 TCRβ、CD4 和 CD8 的 mRNAs 呈负相关。在脓毒症患者中发现 sPD-L1 显着增加。值得注意的是，sPD-L1 与 PD-L1 mRNA 和中性粒细胞标志物相关，并且预示着不良结局。
